Hepatitis web study

Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir + RBV in GT1

TURQUOISE-II

Phase 3

Treatment Naïve and Treatment Experienced

Poordad F, et al. N Engl J Med. 2014;370:1973-82.

Compensated Cirrhosis

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Study Design

TURQUOISE-II: Features

§  Design: Phase 3, randomized, open-label trial evaluating safety and efficacy of 3D (ombitasvir-paritaprevir-ritonavir & dasabuvir) + ribavirin for 12 or 24 weeks in treatment-naïve and experienced patients with chronic HCV GT 1 and compensated cirrhosis

§  Setting: 78 sites in North America and Europe

§  Entry Criteria - Chronic HCV infection with genotype 1 - Treatment-naïve or previously treated with peginterferon + RBV - Age 18-70 - Plasma HCV RNA greater than 10,000 IU/mL - Cirrhosis (Metavir >3, Ishak score >4 or Fibroscan ≥14.6 kPa) - Cirrhosis is compensated (Child-Pugh score <7 at screening) - Absence of coinfection with HBV or HIV

§  Primary End-Point: SVR12

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Regimens

Group A N = 208 3D + Ribavirin

3D + Ribavirin SVR12

SVR12

Group B N = 172

3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir

Drug Dosing Ombitasvir-Paritaprevir-Ritonavir (25/150/100 mg once daily) + Dasabuvir: 250 mg twice daily Ribavirin (RBV): weight-based and divided bid (1000 mg/day if < 75kg or 1200 mg/day if ≥ 75kg)

Week 0 36 12 24

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Results

TURQUOISE II: SVR12 by Genotype 1 Subtype

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

92 89 99 96 94

100

0

20

40

60

80

100

Overall GT1a GT1b

Patie

nts

(%) w

ith S

VR 1

2

3D + RBV x 12 Weeks 3D + RBV x 24 Weeks

191/208 165/172 124/140 114/121 67/68 50/51

3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir; RBV = ribavirin

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Results

TURQUOISE II: SVR12 Based on Prior Treatment

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

94 97 94 87

95 100 100

95

0

20

40

60

80

100

No Prior Treatment Prior Relapser Partial Responder Null Responder

Patie

nts

(%) w

ith S

VR 1

2

3D + RBV x 12 Weeks 3D + RBV x 24 Weeks

81/86 70/74 28/29 23/23 17/18 13/13 65/75 59/62

3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir; RBV = ribavirin

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Results for GT1a

TURQUOISE II: Genotype 1a SVR12 Based on Prior Treatment

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

92.2 93.3 100.0

80.0

92.9 100.0 100.0

92.9

0

20

40

60

80

100

No Prior Treatment Prior Relapser Partial Responder Null Responder

Patie

nts

(%) w

ith S

VR 1

2

3D + RBV x 12 Weeks 3D + RBV x 24 Weeks

59/64 52/56 14/15 13/13 11/11 10/10 40/50 39/42

3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir; RBV = ribavirin

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Results for GT1b

TURQUOISE II: Genotype 1b SVR12 Based on Prior Treatment

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

100.0 100.0

85.7

100.0 100.0 100.0 100.0 100.0

0

20

40

60

80

100

No Prior Treatment Prior Relapser Partial Responder Null Responder

Patie

nts

(%) w

ith S

VR 1

2

3D + RBV x 12 Weeks 3D + RBV x 24 Weeks

22/22 18/18 14/14 10/10 6/7 3/3 25/25 20/20

3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir; RBV = ribavirin

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Adverse Effects

Event 3D + RBV x 12 weeks (n=208)

3D + RBV x 24 weeks (n=172)

Any adverse event (%) 91.8 90.7 Adverse event leading to stopping study drug (%) 1.9 2.3 Any serious adverse event 6.2 4.7 Most common adverse event Fatigue (%) 32.7 46.5 Headache (%) 27.9 30.8 Nausea (%) 17.8 20.3 Pruritis (%) 18.3 19.2 Insomnia (%) 15.4 18.0 Diarrhea (%) 14.4 16.9 Asthenia (%) 13.9 12.8 Rash (%) 11.1 14.5 Irritability (%) 7.2 12.2 Anemia (%) 7.7 10.5 Dyspnea (%) 5.8 12.2 3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir; RBV = ribavirin

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Adverse Effects

Lab Abnormalities 3D + RBV x 12 weeks (n=208)

3D + RBV x 24 weeks (n=172)

Alanine aminotransferase, grade 3 or 4 6 (2.9) 0

Aspartate aminotransferase, grade 3 or 4 1 (0.5) 0

Alkaline phosphatase, grade 3 or 4 0 0

Total bilirubin, grade 3 or 4 28 (13.5) 9 (5.2)

Hemoglobin Grade 1 Grade 2 Grade 3 Grade 4

103 (49.5)

12 (5.8) 2 (1.0) 1 (0.5)

97 (56.4) 18 (10.5)

1 (0.6) 0

3D = Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir; RBV = ribavirin

Source: Poordad F, et al. N Engl J Med. 2014;370:1973-82.

3D + Ribavirin in GT1 and Compensated Cirrhosis TURQUOISE-II: Conclusions

Conclusions: “In this phase 3 trial of an oral, interferon-free regimen evaluated exclusively in patients with HCV genotype 1 infection and cirrhosis, multitargeted therapy with the use of three new antiviral agents and ribavirin resulted in high rates of sustained virologic response. Drug discontinuations due to adverse events were infrequent.”

Hepatitis web study

This slide deck is from the University of Washington’s Hepatitis C Online and Hepatitis Web Study projects.

Hepatitis C Online www.hepatitisc.uw.edu

Hepatitis Web Study http://depts.washington.edu/hepstudy/

Funded by a grant from the Centers for Disease Control and Prevention.